tbuckley/cabot-search huggingface dataset:
Rapid Analysis of Drugs: A Pilot Surveillance System To Detect Changes in the Illicit Drug Supply To Guide Timely Harm Reduction Responses — Eight Syringe Services Programs, Maryland, November 2021–August 2022
Authors: Erin Russell, Edward Sisco, Allison Thomson, Jasmine Lopes, Margaret Rybak, Malik Burnett, Dana Heilman, Meghan G. Appley, R. Matt Gladden
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

A record number of 2,912 drug overdose deaths occurred in Maryland during the 12-month period July 1, 2020-June 30, 2021. Illicitly manufactured fentanyl, fentanyl analogs, or both* were involved in 84% of these deaths.† Timely identification of illicit drug market changes (e.g., fentanyl rapidly replacing heroin) could improve the public health response, specifically communications about risks for novel psychoactive substances. During November 19, 2021-August 31, 2022, the National Institute of Standards and Technology (NIST)§ tested 496 deidentified drug paraphernalia samples that staff members collected at eight Maryland syringe services programs (SSPs), also known as needle exchange programs,¶ in partnership with the Maryland Department of Health Center for Harm Reduction Services (CHRS).** All test results were available within 48 hours. Among the 496 paraphernalia samples collected, 367 (74.0%) tested positive for an opioid, and 364 (99.2%) of these samples contained fentanyl or fentanyl analogs. Approximately four fifths of fentanyl-positive samples also tested positive for the veterinary medicine xylazine, a sedative that when combined with opioids might increase the potential for fatal respiratory depression and soft tissue infections when injected (1). For 248 of the 496 samples, SSP participants also completed a questionnaire about the drugs they had intended to purchase. Among the 212 participants who had intended to buy an opioid, 87.7% were exposed to fentanyl, fentanyl analogs, or both, and 85.8% were unknowingly exposed to xylazine. Results improved awareness of fentanyl and xylazine among SSP staff members and galvanized efforts to enhance SSPs' wound care services for participants experiencing soft tissue injuries possibly associated with injecting xylazine. Rapid analysis of drug paraphernalia can provide timely data on changing illicit drug markets that can be used to mitigate the harms of drug use more effectively.
C5aR1 signaling triggers lung immunopathology in COVID-19 through neutrophil extracellular traps
Authors: Bruna M. Silva, Giovanni F. Gomes, Flavio P. Veras, Seppe Cambier, Gabriel V.L. Silva, Andreza U. Quadros, Diego B. Caetité, Daniele C. Nascimento, Camilla M. Silva, Juliana C. Silva, Samara Damasceno, Ayda H. Schneider, Fabio Beretta, Sabrina S. Batah, Icaro M.S. Castro, Isadora M. Paiva, Tamara Rodrigues, Ana Salina, Ronaldo Martins, Guilherme C.M. Cebinelli, Naira L. Bibo, Daniel M. Jorge, Helder I. Nakaya, Dario S. Zamboni, Luiz O. Leiria, Alexandre T. Fabro, José C. Alves-Filho, Eurico Arruda, Paulo Louzada-Junior, Renê D. Oliveira, Larissa D. Cunha, Pierre Van Mol, Lore Vanderbeke, Simon Feys, Els Wauters, Laura Brandolini, Andrea Aramini, Fernando Q. Cunha, Jörg Köhl, Marcello Allegretti, Diether Lambrechts, Joost Wauters, Paul Proost, Thiago M. Cunha
Journal: Journal of Clinical Investigation (2023)

Patients with severe COVID-19 develop acute respiratory distress syndrome (ARDS) that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that complement component 5a (C5a), through its cellular receptor C5aR1, has potent proinflammatory actions and plays immunopathological roles in inflammatory diseases, we investigated whether the C5a/C5aR1 pathway could be involved in COVID-19 pathophysiology. C5a/C5aR1 signaling increased locally in the lung, especially in neutrophils of critically ill patients with COVID-19 compared with patients with influenza infection, as well as in the lung tissue of K18-hACE2 Tg mice (Tg mice) infected with SARS-CoV-2. Genetic and pharmacological inhibition of C5aR1 signaling ameliorated lung immunopathology in Tg-infected mice. Mechanistically, we found that C5aR1 signaling drives neutrophil extracellular traps-dependent (NETs-dependent) immunopathology. These data confirm the immunopathological role of C5a/C5aR1 signaling in COVID-19 and indicate that antagonists of C5aR1 could be useful for COVID-19 treatment.
An interregional measles outbreak in Spain with nosocomial transmission, November 2017 to July 2018
Authors: Despina Pampaka, Noemí López-Perea, Aurora Fernández-García, Isabel Huertas-Zarco, Maite Castellanos-Martínez, Katja Villatoro-Bongiorno, Javier Roig-Sena, Nuria Torner, María Mar Mosquera, Juan Emilio Echevarría, Joaquim Ferras Prats, Josefa Masa-Calles
Journal: Eurosurveillance (2023)

Given sustained high vaccination coverage and enhanced surveillance for measles, Spain has been free of endemic measles transmission since 2014, achieving elimination certification from the World Health Organization in 2017. In November 2017, measles was introduced through an imported case travelling to the Valencian Community, causing an interregional outbreak. Here, we describe the outbreak using data reported to the national epidemiological surveillance network. The outbreak involved 154 cases (67 males, 87 females) notified in four regions; 148 were laboratory-confirmed and six epidemiologically linked. Most cases were adults aged 30-39 (n = 62, 40.3%) years. Sixty-two cases were hospitalised (40.3%) and 35 presented complications (22.7%). Two thirds of the cases (n = 102) were unvaccinated including 11 infants (≤ 1 year) not yet eligible for vaccination. The main route of transmission was nosocomial; at least six healthcare facilities and 41 healthcare workers and support personnel were affected. Sequencing of the viral nucleoprotein C-terminus (N450) identified genotype B3, belonging to the circulating MVs/Dublin.IRL/8.16-variant. Control measures were implemented, and the outbreak was contained in July 2018. The outbreak highlighted that raising awareness about measles and improving the vaccination coverage in under-vaccinated subgroups and personnel of healthcare facilities are key measures for prevention of future outbreaks.
Inequalities in provision of hip and knee replacement surgery for osteoarthritis by age, sex, and social deprivation in England between 2007–2017: A population-based cohort study of the National Joint Registry
Authors: Erik Lenguerrand, Yoav Ben-Shlomo, Amar Rangan, Andrew Beswick, Michael R. Whitehouse, Kevin Deere, Adrian Sayers, Ashley W. Blom, Andrew Judge
Journal: PLoS Medicine (2023)

Background While the United Kingdom National Health Service aimed to reduce social inequalities in the provision of joint replacement, it is unclear whether these gaps have reduced. We describe secular trends in the provision of primary hip and knee replacement surgery between social deprivation groups. Methods and findings We used the National Joint Registry to identify all hip and knee replacements performed for osteoarthritis from 2007 to 2017 in England. The Index of Multiple Deprivation (IMD) 2015 was used to identify the relative level of deprivation of the patient living area. Multilevel negative binomial regression models were used to model the differences in rates of joint replacement. Choropleth maps of hip and knee replacement provision were produced to identify the geographical variation in provision by Clinical Commissioning Groups (CCGs). A total of 675,342 primary hip and 834,146 primary knee replacements were studied. The mean age was 70 years old (standard deviation: 9) with 60% and 56% of women undergoing hip and knee replacements, respectively. The overall rate of hip replacement increased from 27 to 36 per 10,000 person-years and knee replacement from 33 to 46. Inequalities of provision between the most (reference) and least affluent areas have remained constant for both joints (hip: rate ratio (RR) = 0.58, 95% confidence interval [0.56, 0.60] in 2007, RR = 0.59 [0.58, 0.61] in 2017; knee: RR = 0.82 [0.80, 0.85] in 2007, RR = 0.81 [0.80, 0.83] in 2017). For hip replacement, CCGs with the highest concentration of deprived areas had lower overall provision rates, and CCGs with very few deprived areas had higher provision rates. There was no clear pattern of provision inequalities between CCGs and deprivation concentration for knee replacement. Study limitations include the lack of publicly available information to explore these inequalities beyond age, sex, and geographical area. Information on clinical need for surgery or patient willingness to access care were unavailable. Conclusions In this study, we found that there were inequalities, which remained constant over time, especially in the provision of hip replacement, by degree of social deprivation. Providers of healthcare need to take action to reduce this unwarranted variation in provision of surgery.
<i>Notes from the Field:</i> Posttreatment Lesions After Tecovirimat Treatment for Mpox — New York City, August–September 2022
Authors: Leah Seifu, Elizabeth Garcia, Tristan D. McPherson, Maura Lash, Karen A. Alroy, Mary Foote, Ellen H. Lee, Jeffrey Kwong, Asa Radix, Paul Riska, Jason Zucker, Sarah Zuercher, Marcia Wong
Journal: MMWR Morbidity and Mortality Weekly Report (2023)
Telomere dysfunction in chronic liver disease: The link from aging
Authors: Daniel D. Penrice, Nidhi Jalan-Sakrikar, Diana Jurk, João F. Passos, Douglas A. Simonetto
Journal: Hepatology (2023)

Penrice, Daniel D.; Jalan-Sakrikar, Nidhi; Jurk, Diana; Passos, João F.; Simonetto, Douglas A. Author Information
The tumor microenvironment in the postsurgical liver: Mechanisms and potential targets of postoperative recurrence in human hepatocellular carcinoma
Authors: Junyu Wu, Yau‐Tuen Chan, Yuanjun Lu, Ning Wang, Yibin Feng
Journal: Medicinal Research Reviews (2023)

Surgery remains to be the mainstay of treatment for hepatocellular carcinoma (HCC). Nonetheless, its therapeutic efficacy is significantly impaired by postoperative recurrence, which occurs in more than half of cases as a result of intrahepatic metastasis or de novo tumorigenesis. For decades, most therapeutic strategies on inhibiting postoperative HCC recurrence have been focused on the residual tumor cells but satisfying therapeutic outcomes are barely observed in the clinic. In recent years, a better understanding of tumor biology allows us to shift our focus from tumor cells toward the postoperative tumor microenvironment (TME), which is gradually identified to play a pivotal role in tumor recurrence. In this review, we describe various surgical stress and surgical perturbation on postoperative TME. Besides, we discuss how such alternations in TME give rise to postoperative recurrence of HCC. Based on its clinical significance, we additionally highlight the potential of the postoperative TME as a target for postoperative adjuvant therapeutics.
Erratum for Euro Surveill. 2023;28(15)
Journal: Eurosurveillance (2023)

© This work is licensed under a Creative Commons Attribution 4.0 International License. Closure This is a corrected article applying to the following content: Time to negative throat culture following initiation of antibiotics for pharyngeal group A Streptococcus: a systematic review and meta-analysis up to October 2021 to inform public health control measures
Effects of non-compulsory and mandatory COVID-19 interventions on travel distance and time away from home, Norway, 2021
Authors: Meghana Kamineni, Kenth Engø-Monsen, Jørgen E Midtbø, Frode Forland, Birgitte Freiesleben de Blasio, Arnoldo Frigessi, Solveig Engebretsen
Journal: Eurosurveillance (2023)

BackgroundGiven the societal, economic and health costs of COVID-19 non-pharmaceutical interventions (NPI), it is important to assess their effects. Human mobility serves as a surrogate measure for human contacts and compliance with NPI. In Nordic countries, NPI have mostly been advised and sometimes made mandatory. It is unclear if making NPI mandatory further reduced mobility.AimWe investigated the effect of non-compulsory and follow-up mandatory measures in major cities and rural regions on human mobility in Norway. We identified NPI categories that most affected mobility.MethodsWe used mobile phone mobility data from the largest Norwegian operator. We analysed non-compulsory and mandatory measures with before-after and synthetic difference-in-differences approaches. By regression, we investigated the impact of different NPI on mobility.ResultsNationally and in less populated regions, time travelled, but not distance, decreased after follow-up mandatory measures. In urban areas, however, distance decreased after follow-up mandates, and the reduction exceeded the decrease after initial non-compulsory measures. Stricter metre rules, gyms reopening, and restaurants and shops reopening were significantly associated with changes in mobility.ConclusionOverall, distance travelled from home decreased after non-compulsory measures, and in urban areas, distance further decreased after follow-up mandates. Time travelled reduced more after mandates than after non-compulsory measures for all regions and interventions. Stricter distancing and reopening of gyms, restaurants and shops were associated with changes in mobility.
<i>Notes from the Field:</i> Shiga Toxin-Producing <i>Escherichia coli</i> O157:H7 Linked to Raw Milk Consumption Associated with a Cow-Share Arrangement — Tennessee, 2022
Authors: Christine M. Thomas, Jack H. Marr, Lisa M. Durso, Mugdha Golwalkar, D. J. Irving, Kelly Orejuela, Robin Rasnic, Danny Ripley, Brenda Rue, Linda S. Thomas, Julie Viruez, Mary-Margaret A. Fill, Katie N. Garman, John R. Dunn
Journal: MMWR Morbidity and Mortality Weekly Report (2023)
Clinical Outcomes Following Treatment for COVID-19 With Nirmatrelvir/Ritonavir and Molnupiravir Among Patients Living in Nursing Homes
Authors: Bosco Hon-Ming Ma, Terry Cheuk-Fung Yip, Grace Chung-Yan Lui, Mandy Sze-Man Lai, Elsie Hui, Vincent Wai-Sun Wong, Yee-Kit Tse, Henry Lik-Yuen Chan, David Shu-Cheong Hui, Timothy Chi-Yui Kwok, Grace Lai-Hung Wong
Journal: JAMA Network Open (2023)

Importance Older patients living in nursing homes are at very high risk of mortality after getting COVID-19. Objective To evaluate outcomes following oral antiviral treatment for COVID-19 among nonhospitalized older patients living in nursing homes. Design, Setting, and Participants This is a territory-wide, retrospective cohort study conducted between February 16 and March 31, 2022, with the last follow-up date on April 25, 2022. Participants were patients with COVID-19 living in nursing homes in Hong Kong. Data analysis was performed from May to June 2022. Exposures Molnupiravir, nirmatrelvir/ritonavir, or no oral antiviral treatment. Main Outcomes and Measures The primary outcome was hospitalization for COVID-19, and the secondary outcome was risk of inpatient disease progression (ie, admission to intensive care unit, use of invasive mechanical ventilation, and/or death). Results Of 14 617 patients (mean [SD] age, 84.8 [10.2] years; 8222 women [56.2%]), 8939 (61.2%) did not use oral antivirals, 5195 (35.5%) used molnupiravir, and 483 (3.3%) used nirmatrelvir/ritonavir. Compared with patients who did not use oral antivirals, those who used molnupiravir and nirmatrelvir/ritonavir were more likely to be female and less likely to have comorbid illnesses and hospitalization in the past year. At a median (IQR) follow-up of 30 (30-30) days, 6223 patients (42.6%) were hospitalized and 2307 patients (15.8%) experienced inpatient disease progression. After propensity score weighting, both molnupiravir and nirmatrelvir/ritonavir were associated with a reduced risk of hospitalization (molnupiravir, weighted hazard ratio [wHR], 0.46; 95% CI, 0.37-0.57; P &amp;amp;lt; .001; nirmatrelvir/ritonavir, wHR, 0.46; 95% CI, 0.32-0.65; P &amp;amp;lt; .001) and inpatient disease progression (molnupiravir, wHR, 0.35; 95% CI, 0.23-0.51; P &amp;amp;lt; .001; nirmatrelvir/ritonavir, wHR, 0.17; 95% CI, 0.06-0.44; P &amp;amp;lt; .001). Nirmatrelvir/ritonavir was comparable to molnupiravir in achieving better clinical outcomes (hospitalization, wHR, 1.00; 95% CI, 0.75-1.33; P = .99; inpatient disease progression, wHR, 0.49; 95% CI, 0.20-1.20; P = .12). Conclusions and Relevance In this retrospective cohort study, the use of oral antivirals to treat COVID-19 was associated with a reduced risk of hospitalization and inpatient disease progression among patients living in nursing homes. The findings of this study of nursing home residents could be reasonably extrapolated to other frail older patients living in the community.
Within-patient horizontal transfer of pOXA-48 from a hypervirulent Klebsiella pneumoniae SL218 to Serratia marcescens following spread of the K. pneumoniae isolate among hospitalised patients, Denmark, 2021
Authors: Karen Leth Nielsen, Marc Sørensen, Frederik Boëtius Hertz, Maria Anna Misiakou, Henrik Hasman, Susanne Häussler, Marie Helleberg, Kristian Schønning
Journal: Eurosurveillance (2023)

A hypervirulent Klebsiella pneumoniae SL218 (ST23-KL57), phylogenetically distinct from the classical hypervirulent SL23 (ST23-KL1) lineage, was transmitted between hospitalised patients in Denmark in 2021. The isolate carried a hybrid resistance and virulence plasmid containing blaNDM-1 and a plasmid containing blaOXA-48 (pOXA-48); the latter plasmid was horizontally transferred within-patient to Serratia marcescens. The convergence of drug resistance and virulence factors in single plasmids and in different lineages of K. pneumoniae is concerning and requires surveillance.
Changes in Waivered Clinicians Prescribing Buprenorphine and Prescription Volume by Patient Limit
Authors: Qian Luo, Clese E. Erikson
Journal: JAMA (2023)

This study uses data from a Drug Enforcement Administration list of Drug Addiction Treatment Act (DATA)–waivered clinicians to examine trends in DATA-waivered clinicians’ active participation in prescribing buprenorphine overall and by patient limits between January 2017 and May 2021.
Evaluation of Birth by Cesarean Delivery and Development of Early-Onset Colorectal Cancer
Authors: Yin Cao, Long H. Nguyen, Stefani Tica, Ebunoluwa Otegbeye, Xiaoyu Zong, Bjorn Roelstraete, Andrew T. Chan, Barbara B. Warner, Olof Stephansson, Jonas F. Ludvigsson
Journal: JAMA Network Open (2023)

Importance The incidence of early-onset colorectal cancer (CRC), diagnosed younger than 50 years of age, has increased worldwide. Gut dysbiosis throughout the life course is hypothesized as a leading mechanism, yet epidemiologic data are limited. Objective To prospectively examine the association between birth by cesarean delivery and early-onset CRC among offspring. Design, Setting, and Participants In this population-based, nationwide case-control study in Sweden, adults diagnosed with CRC between 18 and 49 years of age from 1991 to 2017 were identified through the Epidemiology Strengthened by Histopathology Reports in Sweden (ESPRESSO) cohort. Up to 5 general population control individuals without CRC were matched with each case on age, sex, calendar year, and county of residence. Pathology-confirmed end points were linked with the Swedish Medical Birth Register and other national registers. Analyses were conducted from March 2022 through March 2023. Exposure Birth by cesarean delivery. Main Outcomes and Measures The primary outcome was development of early-onset CRC in the overall population and by sex. Results We identified 564 case patients with incident early-onset CRC (mean [SD] age, 32.9 [6.2] years; 284 [50.4%] male) and 2180 matched controls (mean [SD] age, 32.7 [6.3] years; 1104 [50.6%] male). Compared with vaginal delivery, birth by cesarean delivery was not associated with early-onset CRC in the overall population (adjusted odds ratio [aOR], 1.28; 95% CI, 0.91-1.79) after multivariable adjustment for matching and maternal and pregnancy-related factors. A positive association was found for females (aOR, 1.62; 95% CI, 1.01-2.60), but there was no association for males (aOR, 1.05; 95% CI, 0.64-1.72). Conclusions and Relevance In this nationwide, population-based case-control study, birth by cesarean delivery was not associated with early-onset CRC compared with birth by vaginal delivery in the overall population in Sweden. However, females born by cesarean delivery had greater odds of early-onset CRC compared with individuals born through vaginal delivery. This finding suggests that early-life gut dysbiosis may contribute to early-onset CRC in females.
Association of SARS-CoV-2 Antibody Level With Risk of Infection or Hospitalization
Authors: Junyu Long, Peipei Chen, Haitao Zhao
Journal: JAMA Oncology (2023)

Lennard Y. W. Lee, DPhil; Michael Tilby, MBChB; Thomas Starkey, MSci; Maria C. Ionescu, MSc; Alex Burnett, MRCP; Rosie Hattersley, MBChB; Sam Khan, PhD; Martin Little, MRes; Justin K. H. Liu, MRCP; James R. Platt, MRes; Arvind Tripathy, MD; Isabella Watts, BMBCh; Sophie Therese Williams, MSc; Nathan Appanna; Youssra Al-Hajji; Matthew Barnard, PhD; Liza Benny, PhD; Andrew Buckley, PhD; Emma Cattell, PhD; Vinton Cheng, DPhil; James Clark, MBBChir; Leonie Eastlake, BMBS; Kate Gerrand, MSc; Qamar Ghafoor, MBChB; Simon Grumett, PhD; Catherine Harper-Wynne, MD; Rachel Kahn, MSc; Alvin J. X. Lee, PhD; Anna Lydon, MRCP; Hayley McKenzie, PhD; Hari Panneerselvam, MBBS; Jennifer Pascoe, MRCP; Grisma Patel, MRCP; Vijay Patel, MBChB; Vanessa Potter, PhD; Amelia Randle, MRCP; Anne S. Rigg, PhD; Tim Robinson, PhD; Rebecca Roylance, MRCP; Tom Roques, MRCP; Stefan Rozmanowski, MMath; René L. Roux, MRCP; Ketan Shah, DPhil; Martin Sintler, MMedSci; Harriet Taylor; Tania Tillett, MBChB; Mark Tuthill, PhD; Sarah Williams, MRCP; Andrew Beggs, PhD; Tim Iveson, MD; Siow Ming Lee, PhD; Gary Middleton, MD; Mark Middleton, PhD; Andrew S. Protheroe, MD; Matthew W. Fittall, PhD; Tom Fowler, PhD; Peter Johnson, MD; UK COVID Cancer Programme; Emma Kinloch Ms; Emily Lam Ms; Gillian Murphy Ms; Malcolm Rhodes Mr; Kate Robinson Ms; Sanskriti Swarup Ms; Keeley Bernhardt Ms; Jola Bytyci Ms; Yuxin Ying Ms; Sukhmunni Johal Ms; Remarez Sheehan Mr
Deficiency in the omega-3 lysolipid transporter Mfsd2a leads to aberrant oligodendrocyte lineage development and hypomyelination
Authors: Vetrivel Sengottuvel, Monalisa Hota, Jeongah Oh, Dwight L. Galam, Bernice H. Wong, Markus R. Wenk, Sujoy Ghosh, Federico Torta, David L. Silver
Journal: Journal of Clinical Investigation (2023)

Patients with autosomal recessive microcephaly 15 caused by deficiency in the sodium-dependent lysophosphatidylcholine (LPC) transporter major facilitator superfamily domain-containing 2a (Mfsd2a) present with both microcephaly and hypomyelination, suggesting an important role for LPC uptake by oligodendrocytes in the process of myelination. Here we demonstrate that Mfsd2a is specifically expressed in oligodendrocyte precursor cells (OPCs) and is critical for oligodendrocyte development. Single-cell sequencing of the oligodendrocyte lineage revealed that OPCs from OPC-specific Mfsd2a-KO mice (2aOKO mice) underwent precocious differentiation into immature oligodendrocytes and impaired maturation into myelinating oligodendrocytes, correlating with postnatal brain hypomyelination. 2aOKO mice did not exhibit microcephaly, a finding consistent with the notion that microcephaly is the consequence of an absence of LPC uptake at the blood-brain barrier rather than a deficiency in OPCs. Lipidomic analysis showed that OPCs and iOLs from 2aOKO mice had significantly decreased levels of phospholipids containing omega-3 fatty acids, with a corresponding increase in unsaturated fatty acids, the latter being products of de novo synthesis governed by Srebp-1. RNA-Seq indicated activation of the Srebp-1 pathway and defective expression of regulators of oligodendrocyte development. Taken together, these findings indicate that the transport of LPCs by Mfsd2a in OPCs is important for maintaining OPC state to regulate postnatal brain myelination.